Family History 101

If your parents or grandparents had cancer or heart disease, especially if they died from it at an early age, how much does that affect your risk?

People assess their family history in very different ways, and not always rationally. Some feel doomed because they have such an “inheritance.” Others think that even though some close relatives died young, they themselves aren’t at increased risk, since they eat well, stay slim, exercise a lot, and take better care of themselves in general. And still other people think (or at least hope) that they don’t have to worry because their relatives all lived to ripe old ages—despite bad health habits.

It’s often possible to compensate for the worst legacies. Unfortunately, it is also possible to cancel out the effects of even the best genes. Knowing your family medical history is one way to help you take steps to ward off an inherited “fate.”

The fickle finger of fate

Being born with “bad” genes does not seal your fate, except in the case of some relatively rare genetic diseases. And being born with “good” genes doesn’t mean you will never face a disease like cancer, heart disease, or diabetes, of course.

The actress Angelina Jolie is an example of someone whose genetic inheritance cut both ways. She inherited her stunning features primarily from her mother, Marcheline Bertrand. In 2013 Jolie went public about another kind of inheritance from her mother, who died from ovarian cancer in 2007 at age 56—a BRCA genetic mutation, which greatly increases the risk of breast and ovarian cancer. Jolie chose to have a preventive double mastectomy to decrease her risk of breast cancer. Two years later, she underwent a second preventive surgery: the removal of her ovaries and fallopian tubes to decrease her risk of ovarian cancer.

Jolie’s ability to learn about her genes and take action exemplifies the potential promise of genetic research. The science of genetics is a grand advance in knowledge, dazzling in its scope and promise, already with many practical applications in medicine, law, agriculture, pharmacology, and other areas. Though it seems that nearly every week there are reports about new discoveries of genes linked to the risk for various diseases (as well as for more mundane proclivities like food preferences), the science is still very young, and its therapeutic role remains for now largely unfulfilled.

Nature + nurture

Genes are only part of the story. What we do (and don’t do) interacts with what we have inherited. The big killers—notably coronary artery disease, strokes, most cancers, and diabetes—are multifactorial. That is, genes interact with environmental and lifestyle factors, like diet and smoking, to determine whether you will develop certain diseases and when. If such multifactorial disorders run in your family, you merely have an inherited tendency to develop them. In other words, the disorders may never manifest themselves, depending in large part on lifestyle choices you make and environmental factors.

Parents can also pass on or nurture other tendencies by example—eating patterns, attitudes about exercise, and so on. The era we live in and our social stratum also influence our health and habits. For instance, if you are over 60, you grew up at a time when smoking was considered “normal,” unlike today.

The Strange Science of Epigenetics

The Strange Science of Epigenetics

Some of the most exciting genetic research in recent years has focused on what’s called epigenetics—the process by which our genes are “turned on” and “turned off," which in turn affects our risk of disease. Here's a look at the latest findings.

Obesity, which is a contributing factor for many chronic diseases, is an obvious example of a condition in which genes interact with lifestyle and environment. It’s impossible not to notice that obesity runs in families. Part of this is explained by the fact that genes play a large role in aspects of weight regulation, such as the rate at which we burn calories (when at rest and during activity); certain genes may also disrupt appetite control systems in the brain.

Scientists have found a growing list of such genes, which may help explain, for instance, why some people have a seemingly easy time staying thin (despite constant exposure to calorie-dense foods) while others continually struggle with weight gain. What you eat and how active you are matter too, of course, though genetics also influences your preferences for various foods and exercise and how your body responds metabolically.

The Genes-Diet Connection

The Genes-Diet Connection

Genetic factors play a major role in how the things we eat affect our body and our health. Now scientists are gaining insights into how and why this happens.

The “molecules of life”

Genes—collectively our “genome”—are biochemical blueprints we inherit from our parents. Each gene is a discrete segment of DNA (deoxyribonucleic acid) within a chromosome (a long DNA chain containing thousands of genes). They influence every aspect of the body’s development and functioning—from our sex and the color of our eyes and hair to our susceptibility to certain diseases and disorders, and possibly even things like our tendency to be happy—by directing the manufacture of proteins and other molecules.

Only recently have technological developments made it possible to understand more precisely how genes work. One major advance occurred in 2003, when the Human Genome Project finished mapping all the genes in the human body—more than 20,000 of them. This work has led to the discovery of more than 1,800 genes that have disease-related variants and the development of more than 2,000 genetic tests for human conditions. The International HapMap Project is trying to identify genetic links to disease, as well as genetic factors that help explain why certain drugs work better in some people than others and why some people are more (or less) likely to be affected by environmental factors that increase the risk of certain diseases. Another research effort called the Cancer Genome Atlas is developing a complete list of the genes that are associated with cancer and the types of genetic mutations found in cancer cells. Scientists hope to use this research to develop new cancer treatments.

How traits are determined

Normally each cell in the body (except for sperm and eggs) contains the same 46 chromosomes arranged in 23 pairs. Each pair includes one chromosome contributed by the mother via the egg and one by the father via the sperm. A single pair of chromosomes determines the sex of the child. There are two types of sex chromosomes— X and Y. A normal egg always carries an X chromosome, a normal sperm either an X or Y. If their resulting union produces an XX pair, the child will be female; if XY, male. Y chromosomes are much shorter than Xs, so many genes on the X chromosomes go unpaired in males.

A parent passes on a different combination of genes to each child (except for identical twins, who inherit the same genes), which accounts for many differences among siblings.

Some traits are determined by a single pair of genes, others by the interaction of many pairs. Many diseases and disorders are caused, wholly or in part, by genetic mutations.

Genes are usually classified as either dominant or recessive. If a gene is dominant, the feature it determines will be expressed regardless of the character of the gene it is paired with. If the gene is recessive, the trait will appear only if its partner gene matches—that is, only if a child inherits it from both parents. Red hair is one example. A child can be born with red hair only if both parents carry a copy of a recessive gene (on chromosome 16) that affects hair color.

Our genes—and the genetic mutations they may carry—can also increase the risk of developing many diseases, as follows:

Single gene disorders

Relatively few genetic disorders (for example, Huntington’s disease) are caused by a single abnormal dominant gene. If a parent has one of these disorders, there’s a 50-50 chance that a child will. But most serious genetic disorders, such as cystic fibrosis and Tay-Sachs disease, are caused by a pair of abnormal recessive genes, so that the child must inherit one abnormal gene from each parent for the disorder to manifest itself. Otherwise, the normal dominant gene will override the abnormal recessive gene. In that case, the child will be a carrier of the trait, but will not develop the disorder.

Many would-be or expectant parents face choices based on genetic considerations, especially if one parent has an inherited disorder or a close blood relative does. Here are some of the main options for genetic testing, before and during pregnancy.

X-linked (sex-linked) abnormalities

These are caused by a defective recessive gene in an X chromosome and include such disorders as hemophilia and some forms of muscular dystrophy. Because a woman has two X chromosomes, she is much less likely to display any features of an X-linked disease. On the other hand, a man has only one X chromosome, and if he inherits from his mother an X with a mutation that causes muscular dystrophy, for example, he will be affected with the disease, since there is no corresponding gene on the Y chromosome that can express the trait normally.

Red/green color blindness is another example of an X-linked trait. About one in every 12 males has some degree of red/green color blindness, which is passed on by a mother who is a carrier. But only one in every 200 females is color blind, since a woman must inherit the defective X-linked gene from both parents—a color-blind father and a color-blind or carrier mother.

Mutations

These changes in a gene’s DNA can be inherited from a parent or acquired. They often occur when a cell divides and its genetic material is duplicated imperfectly (think of it as something like a typo) and is not repaired. If a mutation occurs during the formation of an egg or sperm that subsequently takes part in fertilization, the mutated gene will end up in all the cells of the resulting embryo. Mutations may also be caused by physical hazards (such as high-energy radiation), chemicals (such as benzene), and infections (such as some viruses)—these are called mutagens. Most genetic mutations are spontaneously corrected or are harmless; others cause birth defects, cancer, or other diseases; some may actually be beneficial.

Inherited mutations and cancer

Two cancers with a strong genetic basis are breast and colorectal cancer.

Breast cancer

BRCA1 and BRCA2 are the best-known “cancer genes,” though it’s actually certain inherited mutations of these genes that greatly increase the risk of cancer. And while BRCA stands for BReast CAncer, these mutations also increase the risk of ovarian, prostate, and other cancers.

Everyone has these two genes, which are involved in normal cell growth and also produce proteins that help repair damaged DNA. If you inherit a mutated version of one of these genes, DNA damage may not be repaired properly, and cells are more likely to develop additional genetic alterations that can lead to cancer.

Both men and women can inherit, be affected by, and pass on BRCA mutations. The child of a carrier of a mutation will have a 50 percent chance of inheriting it. A BRCA mutation can cause problems even though the second copy of the gene is usually normal.

It’s estimated that 5 to 10 percent of breast cancer cases are caused by an inherited mutation; of those, about one-quarter involve a BRCA mutation (as do most hereditary ovarian cancers). Other mutations may also be involved. For instance, in 2014 researchers announced in the New England Journal of Medicine that mutations in a gene called PALB2 also greatly increase the risk of breast cancer, especially in younger women.

By age 70 about 60 percent of women who inherit a BRCA1 mutation and 45 percent of those with a BRCA2 mutation will develop breast cancer, according to the National Cancer Institute (for other women the lifetime risk is about 12 percent).

Men who inherit a BRCA mutation are at greatly increased risk for prostate cancer and, to a lesser degree, breast cancer.

Women and men with a strong family history of breast or ovarian cancer (especially if the cancer occurred at a young age) should be referred for genetic counseling. A 2014 study in the Journal of Community Genetics found that only one or two out of 22 such women actually gets counseling or testing. Women found to carry a BRCA mutation should have annual breast MRIs starting at age 25 and annual mammograms starting at age 30. Because ovarian cancer is hard to detect at an early stage, risk-reducing oophorectomy (removal of the ovaries) is recommended by age 40 or when they plan to have no more children. Screening for ovarian cancer (starting at 30, or possibly younger), while not proven to be effective, should be considered for women who choose not to have an oophorectomy. Women should consider breast-cancer-preventive measures such as tamoxifen or other medication and prophylactic mastectomy, along with oral contraceptives to reduce the risk of ovarian cancer.

Colorectal cancer

About 5 to 10 percent of all cases of colorectal cancer are associated with genetic mutations. Two well-known inherited disorders that increase the risk of colorectal cancer are Lynch syndrome and familial adenomatous polyposis. Lynch syndrome, the most common of these disorders, also increases the risk of endometrial, ovarian, and other cancers. The good news is that low-dose aspirin therapy can reduce the colorectal cancer risk in people with Lynch syndrome. People with a strong family history of colorectal cancer (two or more close family members with the disease, or one who developed it at an early age) should have genetic counseling to determine if testing for hereditary causes of colorectal cancer would be appropriate.

Genetic screening for Alzheimer’s disease

Fewer than 5 percent of people with Alzheimer’s develop the disease before age 65—this is called “early onset.” Most of these cases are caused by an inherited mutation in one of three genes (APP, PSEN1, or PSEN2). Late-onset Alzheimer’s, occurring at age 65 or older, appears to be caused by a combination of genetic, environmental, and lifestyle factors. A specific mutation that causes the late-onset Alzheimer’s has not been found, but researchers have identified several genes (notably APOE-4) that may play a role.

Genetic testing for Alzheimer’s is used primarily in research settings, involving people with a family history of the disease who are taking part in early-detection or prevention studies. Alzheimer’s testing is not recommended for the general population. If you’re found to have a mutation in one of the genes causing early-onset familial Alzheimer’s, there is nothing you can do to prevent or effectively treat the disease. And if you have one of the genes related to the late-onset Alzheimer’s, there’s a good chance you’ll never develop the disease.

This is a limitation to much genetic testing—if you get abnormal results, you’ll become a “patient in waiting,” though you may never develop the disease. Still, some people prefer to learn of such increased risk so they can prepare in advance and perhaps plan their lives differently (retire early, for instance, or decide not to have kids).

The Truth About Home DNA Tests

The Truth About Home DNA Tests

Many people are tempted by ads for at-home (also called direct-to-consumer) genetic tests. They may sound appealing, but there's little or no evidence that the tests are accurate, reliable, or of any practical value for your health.

Who should get genetic testing?

Most people don’t need to consider genetic testing unless they have a close relative who has a hereditary disorder such as cystic fibrosis or are planning pregnancy. In addition, people with a strong family history of breast, ovarian, or colorectal cancer should consider genetic testing.

The first step is to talk with your doctor or other health care provider, who may refer you to a genetic counselor to review your family history and determine if testing is appropriate for you and other family members. People can find a genetic counselor close to home by going to the National Society of Genetic Counselors website. Genetic counselors use their specialized education in both medical genetics and counseling. Genetic counselors can work with you—and your doctor—to help you understand complex genetic information and make informed decisions.

The Genetic Information Nondiscrimination Act prevents health insurers from charging higher premiums to patients who have disease-related genetic mutations. However, it does not prevent providers of life or disability insurance from denying coverage or charging more.

In general, health insurance covers at least some genetic testing. The Affordable Care Act (ACA) specifies that BRCA testing must be covered, with no co-pay or deductible, for women with a strong family history (some plans that existed prior to ACA are exempt from this mandate).

Planting Your Family Tree

Planting Your Family Tree

One of the best gifts you can give your children or grandchildren is a record of your family’s medical tree. Putting all the information you have down in writing can also help you and your doctor evaluate your health risks.